Evidence map›Paper›PMID 41197609›Full record

ReviewNeuron2025

From variants to mechanisms: Neurogenomics in the post-GWAS era.

Michael P Margolis, Miao Tang, Miriam Gagliardi, Cindy Wen, Yeda Wu, Naomi R Wray, Michael J Ziller, Michael J Gandal

Abstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in Neuron, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
  4. Quo Vadis translational neuroscience?Translational neuroscience · 2026
    Review
  5. Genetic and Cortical Cell-Type Liability Architecture of Autism.bioRxiv : the preprint server for biology · 2025
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors.

Michael P MargolisDepartment of Psychiatry and Biobehavioral Sciences, Semel Institute, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90024, USA; Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Miao TangDepartment of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Lifespan Brain Institute at Penn Med and the Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Miriam GagliardiDepartment of Psychiatry, University of Münster, 48149 Münster, Germany; Lab for Genomics of Complex Diseases, Max Planck Institute of Psychiatry, 80804 Munich, Germany.
Cindy WenDepartment of Psychiatry and Biobehavioral Sciences, Semel Institute, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90024, USA; Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Yeda WuDepartment of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Lifespan Brain Institute at Penn Med and the Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Naomi R WrayUniversity of Oxford Department of Psychiatry, Oxford OX3 7JX, UK; The University of Queensland Institute for Molecular Bioscience, Brisbane, QLD 4072, Australia.
Michael J ZillerDepartment of Psychiatry, University of Münster, 48149 Münster, Germany; Center for Soft Nanoscience, University of Münster, 48149 Münster, Germany; Lab for Genomics of Complex Diseases, Max Planck Institute of Psychiatry, 80804 Munich, Germany.
Michael J GandalDepartment of Psychiatry and Biobehavioral Sciences, Semel Institute, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90024, USA; Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Lifespan Brain Institute at Penn Med and the Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA. Electronic address: michael.gandal@pennmedicine.upenn.edu.

Funding

UCLA-Caltech Medical Scientist Training ProgramT32GM008042 · NIGMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI AJIJOLA, OLUJIMI A, DAWSON, DAVID WAYNE · 1985 to 2023
$29.9M
Isoform-level probabilistic transcriptome-wide association to undercover neurogenetic mechanisms underlying complex psychiatric traitsR01MH121521 · NIMH · UNIVERSITY OF PENNSYLVANIA · PI GANDAL, MICHAEL · 2020 to 2024
$3.4M
Population-level and mechanistic dissection of 17q21 structural variant association with psychiatric traitsR01MH123922 · NIMH · UNIVERSITY OF PENNSYLVANIA · PI GANDAL, MICHAEL · 2020 to 2024
$3.1M
Cellular and developmental genetic regulation of 3' isoform diversity in the human brain and its contribution to neuropsychiatric disordersR01MH137578 · NIMH · UNIVERSITY OF PENNSYLVANIA · PI Michael Gandal, Ophir Shalem · 2024 to 2026
$2.1M
Mapping cell type specific isoform diversity in the human brain: dissecting mechanisms of alternative splicing in ASDF30MH135712 · NIMH · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Michael Margolis · 2024 to 2026
$138k
NIGMS NIH HHS T32 GM008042NIMH NIH HHS F30 MH135712NIMH NIH HHS R01 MH121521NIMH NIH HHS R01 MH123922NIMH NIH HHS R01 MH137578
6 · The paper itself

Abstract

Genome-wide association studies (GWASs) have identified thousands of variants associated with neuropsychiatric disorders (NPDs), including autism spectrum disorder (ASD), schizophrenia (SCZ), and Alzheimer's disease (AD). However, deciphering the "causal" biological mechanisms and pathways through which these variants act remains a major obstacle that hinders translational understanding of NPD pathogenesis. NPDs are highly polygenic with contributions from pleiotropic variants across the allelic spectrum, most of which reside within large haplotype blocks in non-coding regions of the genome. Successful mechanistic insight requires identifying disease-relevant cell types and states, mapping variant-to-gene effects, and integrating findings across loci, at scale, to pinpoint pathways of polygenic convergence. Here, we discuss functional genomic, machine learning, and experimental approaches to address each step of this daunting challenge. Ultimately, the convergence of results-across methodologies and within key underlying disease pathways-will be essential to realizing the promise of clinical translation for common, complex brain disorders.

Indexed as

Genetic VariationGenome-Wide Association StudyGenomicsMental DisordersAlzheimer DiseaseAutism Spectrum DisorderGenetic Predisposition to DiseaseHumansMachine LearningMultifactorial InheritanceSchizophrenia

Identifiers

PMID41197609
PMCPMC12626417

What OpenQuestion holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.